Human papillomavirus (HPV) is a sexually transmitted infection that has recently been shown to cause some tonsillar cancers, yet little is known about oral HPV natural history and factors which influence the persistence and progression of these infections into tonsillar cancers. The incidence of oropharyngeal (tonsillar) cancer is increasing the United States and most of these cancers are caused by HPV. People with HIV have a higher rate of oral HPV infection and higher risk of tonsillar cancer. Initial studies suggest antiretroviral therapy does not improve clearance of oral HPV infection. The prevalence of both oral warts (which is caused by HPV) and HPV-associated cancers have not decreased since the introduction of HAART. A prospective study is proposed in which 600 HIV- infected and 400 HIV-uninfected people from the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV Study (WIHS) will be followed every six months for four years. At each visit we will collect cells from participants' mouths using an oral rinse and gargle and test these cells for 37 different types of HPV. We will evaluate how common oral HPV infections are and factors which make it harder to clear these infections. Comparing oral HPV natural history in people with and without HIV will help us to understand the effect that HIV and related immunosupression have on the ability to clear oral HPV infections. PUBLIC HEALTH RELEVANCE: This research is important to understand how long it takes to clear human papillomavirus (HPV) infections in our mouth and throat and what factors make us less likely to clear these infections. Improved survival of HIV-positive individuals due to effective therapies may allow for sufficient time for persistent oral HPV infections to develop into cancer resulting in a continuing increase in HPV-associated tonsillar cancer among those with HIV. It is therefore critical that we understand the effect of HIV infection and immunosupression on oral HPV infection to develop methods to better prevent and screen for these cancers.